CN104788421A - Erdosteine compound for treating respiratory tract inflammation and preparation method of erdosteine compound - Google Patents
Erdosteine compound for treating respiratory tract inflammation and preparation method of erdosteine compound Download PDFInfo
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- 229960003262 erdosteine Drugs 0.000 title claims abstract description 80
- -1 Erdosteine compound Chemical class 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 206010068956 Respiratory tract inflammation Diseases 0.000 title abstract 2
- QGFORSXNKQLDNO-UHFFFAOYSA-N erdosteine Chemical compound OC(=O)CSCC(=O)NC1CCSC1=O QGFORSXNKQLDNO-UHFFFAOYSA-N 0.000 claims abstract description 47
- 239000013078 crystal Substances 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 8
- 229910017488 Cu K Inorganic materials 0.000 claims abstract description 7
- 229910017541 Cu-K Inorganic materials 0.000 claims abstract description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 44
- 238000003756 stirring Methods 0.000 claims description 31
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 30
- 239000000243 solution Substances 0.000 claims description 25
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 22
- 238000002156 mixing Methods 0.000 claims description 17
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 claims description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 16
- 239000012047 saturated solution Substances 0.000 claims description 15
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- NWXMGUDVXFXRIG-WESIUVDSSA-N (4s,4as,5as,6s,12ar)-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O NWXMGUDVXFXRIG-WESIUVDSSA-N 0.000 description 1
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- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- 108010063045 Lactoferrin Proteins 0.000 description 1
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- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical class N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
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- 239000002775 capsule Substances 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
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- 230000001886 ciliary effect Effects 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
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- 238000001727 in vivo Methods 0.000 description 1
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- 239000007924 injection Substances 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 description 1
- 229940078795 lactoferrin Drugs 0.000 description 1
- 235000021242 lactoferrin Nutrition 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/36—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Abstract
The invention discloses an erdosteine compound for treating respiratory tract inflammation and a preparation method of the erdosteine compound, belonging to the technical field of medicines. The X-ray powder diffraction patterns of the erdosteine compound measured by using Cu-K alpha rays are shown as the Figure 1. The erdosteine crystal provided by the invention is stable in chemical properties and high in water solubility, has high stability, brings convenience to various preparations and is very suitable for clinical application.
Description
Technical field
The present invention relates to field of medicaments, relate to a kind of Erdosteine compound for the treatment of respiratory inflammation and preparation method thereof.
Background technology
Phlegm is the product of respiratory inflammation, can stimulate respiratory mucosa, causes cough and asthma, and can increase the weight of to infect.When acute/chronic bronchitis or chronic lung diseases respiratory insufficiency, spend height as patient's thick sputum or form phlegm bolt, can clogs airways and cause suffocating.Therefore, use sticky phlegm conditioning agent, make patient's phlegm dissolving, thinning, viscosity reduces, and accelerate respiratory mucosa ciliary movement, improve transport function, tool is of great significance.
This is smooth etc. for the sticky phlegm conditioning agent of current listing such as bromhexine, mesna, carboxylic first, all has sticky phlegm regulating effect in various degree, but its pharmacology or there are some defects clinically.Sulfydryl free in molecular structure can adsorb gi tract Saliva Orthana, gi tract local damage can be produced after oral, side effect is larger, the anti-microbial activity of penicillin, cephalosporin analog antibiotic, erythromycin, tsiklomitsin etc. can be weakened, unsuitable drug combination, not high to the improvement effect of some respiration parameter as phlegm viscosity etc.
Erdosteine is a kind of prodrug, with the sulfydryl closed of non-free in its structure, to local Saliva Orthana inactive, after oral through metabolism produce three containing free sulfhydryl groups meta-bolites and play pharmacological action, thus oral rear without obvious gastrointestinal side effect.Experiment proves; Erdosteine cylinder metabolism-ure can make mucinous disulfide bonds in bronchial secretion; and change secretory product composition and rheological property; reduce sputum viscosity; improve downtrod respiratory function; this product energy scavenging free radicals, the oxidation deactivation that available protecting a1-antitrypsin brings out from cigarette, dirt, prevents the damage to lung elastance albumen and neutrophil leucocyte.This product obviously can also increase IgA/ albumin, lactoferrin/albuminous ratio, weakens local inflammation, strengthens and improves the osmosis of microbiotic to tunica mucosa bronchiorum, be conducive to the treatment of the various inflammation of respiratory tract.External clinical clinical studies show: with like product as acetylcysteine, this is smooth for carboxylic first, Transbroncho etc. compares, this product has good curative effect to acute/chronic bronchitis, more effective to the improvement of some respiratory function parameter, there is not drug accumulation in heavy dose of administration, Liver and kidney function moderate obstacle to this product characteristics of pharmacokinetics without obvious change.
Erdosteine water-soluble poor, effective bioavailability in human body is low, and medicine in vivo absorption rate usually determined by the speed dissolved, medicine in solid preparation is before being absorbed, have to pass through disintegration and dissolve the process then transferring solution to, if medicine not easily discharges from preparation or the dissolution rate of medicine is very slow, then the absorption rate of said preparation Chinese traditional medicine or degree just likely have problems.
The approach of existing solution Erdosteine poorly water-soluble mainly comprises change formulation, as CN101606931B is made into dispersible tablet, although above-mentioned preparation improves the water-soluble of medicine to a certain extent, also there is many defects.Therefore, the Erdosteine compound that a kind of improved performance is provided is necessary.
The present inventor starts with from the research of Erdosteine solid chemical material existence, a kind of Erdosteine compound crystal has been prepared through a large amount of tests, surprisingly find through overtesting, this compound crystal significantly improves its solvability, has higher stability.
Summary of the invention
Primary goal of the invention of the present invention is to propose a kind of Erdosteine compound for the treatment of respiratory inflammation.
Second goal of the invention of the present invention is the preparation method proposing above-mentioned Erdosteine compound.
In order to realize object of the present invention, the technical scheme of employing is:
A kind of Erdosteine compound, is characterized in that, the X-ray powder diffraction pattern that described Erdosteine compound uses the measurement of Cu-K alpha-ray to obtain as shown in Figure 1.
The preparation method of Erdosteine compound of the present invention is:
(1) Erdosteine crude product is ground, cross 100 ~ 200 mesh sieves, then join in the mixing solutions of Virahol and propyl formate, stir 15 ~ 25 minutes;
(2) add the mixing solutions of tetrahydrofuran (THF), water under stirring, be warming up to 20-45 DEG C simultaneously;
(3), after solution adds, leave standstill 2-3 hour, drip sodium chloride saturated solution under the condition of stirring, at the uniform velocity dropwise in 0.5h;
(4) be added dropwise to complete rear cooling, continue to stir 0.5-2h, leave standstill 2-4h crystallize out, filter, vacuum-drying obtains Erdosteine crystal.
Wherein, in step (1), the volume of Virahol and propyl formate mixing solutions is 3-5 times of Erdosteine weight, and the volume ratio of Virahol and propyl formate is 1:4.5; Step (1) described stirring velocity is 80-120 rev/min, and step (2) described stirring velocity is 430-560 rev/min, and step (3) described stirring velocity is 80-120 rev/min, and step (4) described stirring velocity is 10-15 rev/min; The mixed liquor volume of tetrahydrofuran (THF), water described in step (2) is 8-12 times of Erdosteine weight, tetrahydrofuran (THF): water volume ratio is 1:3.5; Described in step (3), the temperature of sodium chloride saturated solution is-15 DEG C-5 DEG C; The volume of sodium chloride saturated solution described in step (3) is 5-8 times of Erdosteine weight; Step is cooled to-15 DEG C-5 DEG C in (4).
Below summary of the invention of the present invention is further described:
Erdosteine compound of the present invention, uses the X-ray powder diffraction of Cu-K α 1 radionetric survey as shown in Figure 1.
This Erdosteine crystalline compounds is prepared from by the following method:
(1) Erdosteine crude product is ground, cross 100 ~ 200 mesh sieves, then join in the mixing solutions of Virahol and propyl formate, stir 15 ~ 25 minutes;
(2) add the mixing solutions of tetrahydrofuran (THF), water under stirring, be warming up to 20-45 DEG C simultaneously;
(3), after solution adds, leave standstill 2-3 hour, drip sodium chloride saturated solution under the condition of stirring, at the uniform velocity dropwise in 0.5h;
(4) be added dropwise to complete rear cooling, continue to stir 0.5-2h, leave standstill 2-4h crystallize out, filter, vacuum-drying obtains Erdosteine crystal.
By mixed solvent Virahol and propyl formate, the volume of preferred Virahol and propyl formate mixing solutions is 3-5 times of Erdosteine weight, and the volume ratio of Virahol and propyl formate is 1:4.5.After the mixing solutions of this ratio is by Erdosteine dissolution of solid, then under the stirring velocity of 430-560 rev/min, add the mixing solutions of tetrahydrofuran (THF), water, be warming up to 20-45 DEG C simultaneously.Finally use sodium chloride saturated solution, the temperature of preferred sodium chloride saturated solution is-15 DEG C-5 DEG C, amasss the 5-8 times of recrystallization into Erdosteine weight, and cooling crystallize out, filtering vacuum drying obtains Erdosteine crystalline compounds.The water-soluble Erdosteine solid compared to existing technology of this Erdosteine crystalline compounds, its solubility property increases, and stability and other performances also keep good.
The Erdosteine crystal preparation of gained can be become different formulations.Can be oral preparations or liquid preparation, described oral preparations be conventional tablet, capsule, granule etc., and described liquid preparation is oral liquid, freeze-dried powder, injection liquid etc.Relative proportions those skilled in the art between the auxiliary material that various formulation is used and each component can go adjustment according to the actual requirements.
The stable chemical nature of Erdosteine crystal provided by the invention, water-solublely improves a lot, and has higher stability, to the convenience that the preparation of various preparation brings.
accompanying drawing illustrates:
Fig. 1 is the X-ray powder diffraction pattern of Erdosteine compound prepared by embodiment 1.
Embodiment
The specific embodiment of the present invention is only limitted to explain further and the present invention is described, does not limit Composition of contents of the present invention.
embodiment 1:the preparation of Erdosteine compound
(1) ground by Erdosteine crude product, cross 100 mesh sieves, then joining volume is that in the Virahol of 3 times of Erdosteine weight and the mixing solutions of propyl formate, the volume ratio of Virahol and propyl formate is 1:4.5, and 80 revs/min are stirred 15 minutes;
The tetrahydrofuran (THF) that volume is 8 times of Erdosteine weight is added: water volume ratio is the mixing solutions of 1:3.5, is warming up to 20 DEG C simultaneously under (2) 430 revs/min of stirrings;
(3) after solution adds, leave standstill 2 hours, drip the sodium chloride saturated solution of-15 DEG C under 80 revs/min of conditions stirred, the volume of sodium chloride saturated solution is 5 times of Erdosteine weight, at the uniform velocity dropwises in 0.5h;
(4) be cooled to-15 DEG C DEG C after being added dropwise to complete, continue to stir 0.5h under the stir speed (S.S.) of 10 revs/min, leave standstill 2h crystallize out, filter, vacuum-drying obtains Erdosteine crystal.
This compound crystal detects through high performance liquid chromatography, and purity is 99.99%, yield 98.3%; The X-ray powder diffraction pattern that the measurement of use Cu-K alpha-ray obtains as shown in Figure 1.
embodiment 2:the preparation of Erdosteine compound
(1) ground by Erdosteine crude product, cross 150 mesh sieves, then joining volume is that in the Virahol of 4 times of Erdosteine weight and the mixing solutions of propyl formate, the volume ratio of Virahol and propyl formate is 1:4.5, and 100 revs/min are stirred 20 minutes;
The tetrahydrofuran (THF) that volume is 10 times of Erdosteine weight is added: water volume ratio is the mixing solutions of 1:3.5, is warming up to 33 DEG C simultaneously under (2) 495 revs/min of stirrings;
(3) after solution adds, leave standstill 2.5 hours, drip the sodium chloride saturated solution of-5 DEG C under 100 revs/min of conditions stirred, the volume of sodium chloride saturated solution is 6.5 times of Erdosteine weight, at the uniform velocity dropwises in 0.5h;
(4) be cooled to-5 DEG C DEG C after being added dropwise to complete, continue to stir 1.3h under the stir speed (S.S.) of 12.5 revs/min, leave standstill 3h crystallize out, filter, vacuum-drying obtains Erdosteine crystal.
This compound crystal detects through high performance liquid chromatography, and purity is 99.99%, yield 98.3%; The X-ray powder diffraction pattern that the measurement of use Cu-K alpha-ray obtains as shown in Figure 1.
embodiment 3:the preparation of Erdosteine compound
(1) ground by Erdosteine crude product, cross 200 mesh sieves, then joining volume is that in the Virahol of 5 times of Erdosteine weight and the mixing solutions of propyl formate, the volume ratio of Virahol and propyl formate is 1:4.5, and 120 revs/min are stirred 25 minutes;
The tetrahydrofuran (THF) that volume is 12 times of Erdosteine weight is added: water volume ratio is the mixing solutions of 1:3.5, is warming up to 45 DEG C simultaneously under (2) 560 revs/min of stirrings;
(3) after solution adds, leave standstill 3 hours, drip the sodium chloride saturated solution of 5 DEG C under 120 revs/min of conditions stirred, the volume of sodium chloride saturated solution is 8 times of Erdosteine weight, at the uniform velocity dropwises in 0.5h;
(4) be cooled to 5 DEG C after being added dropwise to complete, continue to stir 2h under the stir speed (S.S.) of 15 revs/min, leave standstill 4h crystallize out, filter, vacuum-drying obtains Erdosteine crystal.
This compound crystal detects through high performance liquid chromatography, and purity is 99.99%, yield 98.3%; The X-ray powder diffraction pattern that the measurement of use Cu-K alpha-ray obtains as shown in Figure 1.
experimental example 1:the stability test of product of the present invention
1, accelerated test
Three batches of products of Example 1, in temperature be 40 ± 2 DEG C, relative humidity be the condition of 75 ± 5% under place 6 months, respectively at 0,1,2,3,6 the end of month sampling once, measure, in table 1 by high spot reviews project.
Table 1, accelerated test result (temperature 40 ± 2 DEG C, relative humidity 75% ± 5%)
Result shows, this product temperature be 40 ± 2 DEG C, relative humidity be 75 ± 5% conditions under place 6 months, its related substances is low, and each index has no significant change, and this product quality stability is good.
2, test of long duration
Example 1 product, in temperature be 25 DEG C, relative humidity be 60% ± 10% place, respectively at 0,3,6,9,12,18,24 the end of month sampling and measuring.Measure proterties, content and related substance according to relevant regulations under " quality standard " item, record result (the results are shown in following table 2), and compare with criticizing to record for 0 month.
Table 2, long-term test results (temperature 25 ± 2 DEG C, relative humidity 60% ± 5%)
Shown by long-term test results: Erdosteine compound of the present invention is 25 ± 2 DEG C in temperature, relative humidity is place under the condition of 60% ± 5% to stablize for 24 months, and indices is without considerable change.
Other embodiments are also through as above accelerating and stability test, and result is similar to embodiment 1.
experimental example 2:
The water-soluble experiment of the Erdosteine compound of embodiment of the present invention 1-3, compared with commercially available Erdosteine.Specific experiment method is: in the low capacity bottle of constant temperature jacket, add appropriate distilled water, Erdosteine is added to no longer dissolving at 25 DEG C, start magnetic stirrer, Keep agitation under constant temperature, in experimentation, system is in the state of two-phase coexistent all the time, after 70 minutes system liquid phase in the concentration of Erdosteine be solubleness at this temperature.Carry out sampling analysis after 2 hours, get the close mean value of adjacent two times result as measured value of experiment, before sampling, in order to make solid-liquid fully be separated, after stopping stirring, not molten Erdosteine is deposited to the bottom of low capacity bottle, extract a small amount of upper clear supernate with syringe, filter with the filter of 0.45 micron, sample thief from filtrate, the content of Erdosteine is measured, specifically in table 3 by HPLC.
Under table 3 room temperature, Erdosteine compound of the present invention is water-soluble
In analysis, table is known, and compared with prior art, the water-soluble of Erdosteine compound provided by the invention is improved greatly.
Claims (8)
1. treat an Erdosteine compound for respiratory inflammation, it is characterized in that: the X-ray powder diffraction pattern that described Erdosteine compound uses the measurement of Cu-K alpha-ray to obtain as shown in Figure 1.
2. Erdosteine compound according to claim 1, is characterized in that: the preparation method of described Erdosteine compound is:
(1) Erdosteine crude product is ground, cross 100-200 mesh sieve, then join in the mixing solutions of Virahol and propyl formate, stir 15-25 minute;
(2) add the mixing solutions of tetrahydrofuran (THF), water under stirring, be warming up to 20-45 DEG C simultaneously;
(3), after solution adds, leave standstill 2-3 hour, drip sodium chloride saturated solution under the condition of stirring, at the uniform velocity dropwise in 0.5h;
(4) be added dropwise to complete rear cooling, continue to stir 0.5-2h, leave standstill 2-4h crystallize out, filter, vacuum-drying obtains Erdosteine crystal.
3. Erdosteine compound according to claim 2, is characterized in that: in step (1), and the volume of Virahol and propyl formate mixing solutions is 3-5 times of Erdosteine weight, and the volume ratio of Virahol and propyl formate is 1:4.5.
4. Erdosteine compound according to claim 2, it is characterized in that: step (1) described stirring velocity is 80-120 rev/min, step (2) described stirring velocity is 430-560 rev/min, step (3) described stirring velocity is 80-120 rev/min, and step (4) described stirring velocity is 10-15 rev/min.
5. Erdosteine compound according to claim 2, is characterized in that: the mixed liquor volume of tetrahydrofuran (THF), water described in step (2) is 8-12 times of Erdosteine weight, tetrahydrofuran (THF): water volume ratio is 1:3.5.
6. Erdosteine compound according to claim 2, is characterized in that: described in step (3), the temperature of sodium chloride saturated solution is-15 DEG C-5 DEG C.
7. Erdosteine compound according to claim 2, is characterized in that: the volume of sodium chloride saturated solution described in step (3) is 5-8 times of Erdosteine weight.
8. Erdosteine compound according to claim 2, is characterized in that: step is cooled to-15 DEG C-5 DEG C in (4).
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610595315.4A CN106187992A (en) | 2015-04-30 | 2015-04-30 | A kind of method of the erdosteine compound preparing treatment respiratory inflammation |
| CN201510215321.8A CN104788421B (en) | 2015-04-30 | 2015-04-30 | A kind of erdosteine compound treating respiratory inflammation and preparation method thereof |
| CN201610595340.2A CN106220604A (en) | 2015-04-30 | 2015-04-30 | A kind of method of the erdosteine compound preparing treatment respiratory inflammation |
| CN201610595356.3A CN106146456A (en) | 2015-04-30 | 2015-04-30 | A kind of method of the erdosteine compound preparing treatment respiratory inflammation |
| CN201610595361.4A CN106220605A (en) | 2015-04-30 | 2015-04-30 | A kind of method of the erdosteine compound preparing treatment respiratory inflammation |
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| CN201510215321.8A CN104788421B (en) | 2015-04-30 | 2015-04-30 | A kind of erdosteine compound treating respiratory inflammation and preparation method thereof |
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| CN201610595340.2A Division CN106220604A (en) | 2015-04-30 | 2015-04-30 | A kind of method of the erdosteine compound preparing treatment respiratory inflammation |
| CN201610595356.3A Division CN106146456A (en) | 2015-04-30 | 2015-04-30 | A kind of method of the erdosteine compound preparing treatment respiratory inflammation |
| CN201610595361.4A Division CN106220605A (en) | 2015-04-30 | 2015-04-30 | A kind of method of the erdosteine compound preparing treatment respiratory inflammation |
| CN201610595315.4A Division CN106187992A (en) | 2015-04-30 | 2015-04-30 | A kind of method of the erdosteine compound preparing treatment respiratory inflammation |
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| CN201610595361.4A Withdrawn CN106220605A (en) | 2015-04-30 | 2015-04-30 | A kind of method of the erdosteine compound preparing treatment respiratory inflammation |
| CN201510215321.8A Expired - Fee Related CN104788421B (en) | 2015-04-30 | 2015-04-30 | A kind of erdosteine compound treating respiratory inflammation and preparation method thereof |
| CN201610595315.4A Withdrawn CN106187992A (en) | 2015-04-30 | 2015-04-30 | A kind of method of the erdosteine compound preparing treatment respiratory inflammation |
| CN201610595356.3A Withdrawn CN106146456A (en) | 2015-04-30 | 2015-04-30 | A kind of method of the erdosteine compound preparing treatment respiratory inflammation |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104983693A (en) * | 2015-08-13 | 2015-10-21 | 青岛蓝盛洋医药生物科技有限责任公司 | Medicine erdosteine composition granules for treating respiratory tract infection |
| CN105078901A (en) * | 2015-09-10 | 2015-11-25 | 青岛蓝盛洋医药生物科技有限责任公司 | Erdosteine pharmaceutical composition dry suspension for treating diseases of respiratory system |
| CN106187991A (en) * | 2016-07-19 | 2016-12-07 | 山东罗欣药业集团股份有限公司 | A kind of compound treating respiratory system disease and preparation method thereof |
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| IT202000016816A1 (en) | 2020-07-10 | 2022-01-10 | Edmond Pharma Srl | COMPOSITIONS INCLUDING ANTIOXIDANT COMPOUNDS AS AID IN THE TREATMENT OF VIRAL INFECTIONS |
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| CN1303065C (en) * | 2004-05-20 | 2007-03-07 | 江苏豪森药业股份有限公司 | Ambroxol cysteine analogs and their preparation process and use thereof |
| EP2060568B1 (en) * | 2007-11-16 | 2011-10-05 | Edmond Pharma S.R.L. | Polymorphs of enantiopure erdosteine |
| CN101941963A (en) * | 2010-04-22 | 2011-01-12 | 浙江康乐药业股份有限公司 | Synthesis method of erdosteine |
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2015
- 2015-04-30 CN CN201610595340.2A patent/CN106220604A/en not_active Withdrawn
- 2015-04-30 CN CN201610595361.4A patent/CN106220605A/en not_active Withdrawn
- 2015-04-30 CN CN201510215321.8A patent/CN104788421B/en not_active Expired - Fee Related
- 2015-04-30 CN CN201610595315.4A patent/CN106187992A/en not_active Withdrawn
- 2015-04-30 CN CN201610595356.3A patent/CN106146456A/en not_active Withdrawn
Non-Patent Citations (1)
| Title |
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| 李飞等: "厄多司坦的合成", 《中国医药工业杂志》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104983693A (en) * | 2015-08-13 | 2015-10-21 | 青岛蓝盛洋医药生物科技有限责任公司 | Medicine erdosteine composition granules for treating respiratory tract infection |
| CN105078901A (en) * | 2015-09-10 | 2015-11-25 | 青岛蓝盛洋医药生物科技有限责任公司 | Erdosteine pharmaceutical composition dry suspension for treating diseases of respiratory system |
| CN106187991A (en) * | 2016-07-19 | 2016-12-07 | 山东罗欣药业集团股份有限公司 | A kind of compound treating respiratory system disease and preparation method thereof |
| CN106187991B (en) * | 2016-07-19 | 2019-04-30 | 山东罗欣药业集团股份有限公司 | A kind of compound and preparation method thereof for treating respiratory disease |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104788421B (en) | 2016-08-24 |
| CN106187992A (en) | 2016-12-07 |
| CN106220604A (en) | 2016-12-14 |
| CN106146456A (en) | 2016-11-23 |
| CN106220605A (en) | 2016-12-14 |
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